Melanoma is responsible for only 2.3% of all skin cancers, but it is the most life threatening form, being responsible for over 75% of skin cancer deaths. Cutaneous melanoma is currently a major public health concern due to rising incident rates worldwide, claiming the lives of more than 2000 individuals in the UK alone each year. The rate of increase is higher than for any other cancer and it has been likened to an epidemic. Some of the increase may be due to improvements in surveillance and early detection as well as changes in diagnostic criteria, however, it is considered that a substantial proportion of the increase is real. The increase has been linked to a rise in sun exposure and/or increased used of artificial sunbeds.
European age-standardized incident rates have increased 4-fold for woman and 7-fold for men over the last 30 years. Melanoma is now the fifth most common cancer in the UK, accounting for 4% of all new cancer cases. Mortality rates have also increased, but at a rate disproportionately less than incidence, such that the ratio of deaths to patient cases as fallen steadily over the last 50 years. Even so, melanoma accounts for nearly 50,000 deaths annually, worldwide.
Factors that affect prognosis include the thickness of the tumor in millimeters (Breslow's depth), the depth related to skin structures (Clark level), the type of melanoma, the presence of metastasis and the presence of ulceration. Primary melanomas which demonstrate epidermal ulceration at the time of diagnosis predicts increased rates of metastasis and poorer outcomes compared to non-ulcerated tumours. However, the underlying biology of ulceration remains enigmatic.
Treatment of early stage (AJCC stage 1a or 1b) melanoma involves the removal of the tissue surrounding the melanoma, known as a wide local excision. This is typically followed by regular examination of the patient for the recurrence of disease over a period of 1-5 years. Therapy, such as chemotherapy, is not given to patients with early stage melanoma.
For patients with thicker tumours (AJCC stage 2a, 2b or 2c) a wide local excision may be followed by a sentinel lymph node biopsy to determine whether the disease has spread to the lymph nodes. If it has, a lymph node dissection may be performed. Treatment after surgery to help prevent the melanoma from returning or spreading is known as adjuvant therapy. Adjuvant therapy may be chemotherapy or biological therapy (e.g. interferon treatment). However, adjuvant therapy is generally only offered to patients with stage 2 melanoma as part of a clinical trial.
Chemotherapy, radiotherapy and/or biological therapy may be used to treat recurring melanomas in patients who have had a stage 2 tumour removed, to help control further metastatic progression in patients with disease confined to lymph nodes (stage 3) or to shrink melanomas in patients with advanced metastatic disease (AJCC stage 4) in order to reduce symptoms.
There remains a need to improve treatment of patients suffering from melanoma and to decrease the likelihood of progression to metastasis.
It is an aim of some embodiments of the present invention to at least partially mitigate some of the problems identified in the prior art.